Identification of key gene for improvement of multiple sclerosis treatments

Karl Carlström and Fredirk Piehl. Photo: Stefan Zimmermann

CMM researcher Karl Carlström and colleagues have found that the Gsta4 gene functions as a protector of oligodendrocytes, the cell type that is destroyed by the immune system in patients with multiple sclerosis (MS). Among the coauthors of the paper, Keying Zhu, Ewoud Ewing, Robert A. Harris, Maja Jagodic and Fredrik Piehl (last author) are also researchers at CMM.

The study, which was recently published in Nature Communications, shows that Gsta4 mediates the maturation process in oligodendrocytes in rats and is needed for the effect of some known and future MS drugs.

Oligodendrocytes are found in the central nervous system and produce lipid-rich myelin sheets surrounding and insulating nerve axons. Immune attacks on the myelin, destruction of oligodendrocytes and the nerves, eventually leads to disability in individuals affected by MS.

Through experiments with a rat model of MS the researchers found that high levels of Gsta4 seem to speed up the maturation, promote repair and prevent apoptotic death signaling in damaged oligodendrocytes.

During the progressive stage of MS, oligodendrocytes and neurons in the brain die without re-forming. The experimental results presented in this paper can shed light on the mechanisms behind disease progression, but also on the mechanism of action of the drugs in use, or soon to be used, for MS.

A more detailed summary of the study is found on the KI webpage 

Publication:

“Gsta4 controls apoptosis of differentiating adult oligodendrocytes during homeostasis and remyelination via the mitochondria-associated Fas-Casp8-Bid-axis.” Karl E Carlström, Keying Zhu, Ewoud Ewing, Inge E Krabbendam, Robert A Harris, Ana Mendanha Falcão, Maja Jagodic, Gonçalo Castelo-Branco and Fredrik Piehl. Nature Communications, online 13 August 2020, doi 10.1038/s41467-020-17871-5.